Nanoparticles are useful in the stabilization and delivery of drugs: they improve solubility, extend shelf lives, reduce side effects and sustain drug exposure for a prolonged therapeutic effect. The matrix used for targeted drug delivery is usually composed of lipids, polymers or metals and assembled into vesicles, micelles or particles. See Torchilin V. (2006) Adv Drug Deliv. 58:1532; Stark W (2011) Angew Chem Int Ed. 50: 1242; Sous san E et al. (2009) ACIE. 48: 274. The main independent particle variables that determine the in vivo applicability include size, surface charge, and dispersibility, mainly governed by the hydrophobic effect. Nel A et al. (2009) Nat. Matter. 8: 543. In contrast to these classical carrier materials, it is exceedingly difficult to design a colloidal delivery system exclusively from amino acids, mainly due to solubility issues of short hydrophobic peptides.
The dissolution of hydrophobic peptides is tedious and thus often requires elaborate protocols of solvent addition [14]. Despite all efforts, many hydrophobic peptides are not soluble at all and consequently difficult to synthesize by Fmoc- or Boc-protection group chemistry: peptide precipitation on the solid phase during synthesis leads to small yields and dominant quantities of by-products.
Yet a particle matrix composed of peptides is desirable as it can degrade into single amino acids. In addition, unlike other matrix materials, e.g., polymer, products of peptide synthesis can be purified to up to 98%, avoiding molecular polydispersity and thus issues with the reproducibility of physicochemical properties. Further, properties of peptide structure can be readily modulated, e.g., by introduction of amino acid point mutations. Accordingly, there is still a strong need for engineering a degradable drug carrier, which can be synthesized and purified in a simple process.